22. The Diels-Alder Cycloaddition Reaction

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1 22. The Diels-Alder Cycloaddition Reaction A. Introduction In 1928, tto Diels and his student Kurt Alder at the University of Kiel in Germany first reported their work in the reactions of electron poor alkenes with electron rich dienes to form substituted cyclohexenes. The importance of this reaction was realized over the course of the next 22 years and in 1950, Diels and Alder were awarded the Nobel Prize in chemistry. The Diels-Alder reaction is also known as a [4 2] cycloaddition because it involves the concerted (no intermediate) reaction of a four-atom system with a two-atom system via a cyclic transition state. The four-atom molecule is a diene, while the two-atom molecule is a dienophile (alkene or alkyne). The product of the Diels-Alder reaction is a 6-membered ring containing a double bond (cyclohexene). The preparation of cyclic molecules is a difficult task in organic chemistry, which reveals why the Diels-Alder reaction is so synthetically useful. diene dienophile Cyclic Diels-Alder Transition Product State Figure 1. The Diels-Alder Reaction The Diels-Alder reaction shown above between butadiene and ethene is the simplest example and is useful in showing how the atoms come together. In practice, however, this specific case does not work all that well. Diels-Alder reactions work best when the dienophile contains one or more electron withdrawing groups as shown in figure 2. Room Temp Some Electron ithdrawing Groups () C R C R Figure 2. Diels-Alder Reaction with Electron ithdrawing Group on the Dienophile The Diels-Alder reaction requires that the diene be oriented in the s-cis conformation for the reaction to take place. Acyclic dienes favors the lower energy s-trans conformation. A small equilibrium with the s-cis conformation does, however, exist, which is enough to allow the Diels- Alder reaction to take place. In the case of cyclic dienes, the diene is locked in the necessary s- cis conformation. For this reason, cyclic dienes are especially reactive in Diels-Alder reactions. s-trans s-cis Figure 3. s-cis and s-trans Dienes locked in the s-cis conformation Experiment 22 The Diels-Alder Cycloaddition Reaction pg. 1

2 hen a cyclic diene is used in a Diels-Alder reaction, a second ring is formed providing a bicyclic product. As shown in figure 4, when cyclopentadiene is reacted with a dienophile, a new six-membered ring is formed while the original five-membered ring is still present and becomes part of a bridged bicyclic system. The product can be drawn as a flat representation or a more accurate three-dimensional representation. NC = Figure 4. Diels-Alder Reaction Producing a Bicyclic Product In this laboratory experiment, you will be using cyclopentadiene and maleic anhydride in a Diels- Alder reaction. This reaction can produce two stereochemically different products: an endo product and an exo product. In most cases, such as in the reaction below, the endo product is formed more rapidly and is thus the favored product. cyclopentadiene maleic anhydride H H endo Good Yield H H exo Not Formed Figure 5. The Diels-Alder Reaction of Cyclopentadiene ith Maleic Anhydride The endo and exo products can be rationalized by looking at both the endo and exo addition of the dienophile. In the endo addition the dienophile adds to the diene in such a way that the carbonyl substituents are inside or directly under the diene π-system during the addition. In the exo addition, the carbonyl substituents are outside and there is no overlap between these groups and the diene π-system during the addition process. The exact reasons for the endo preference will not be discussed here. endo addition exo addition Figure 6. Endo vs Exo Addition Cyclopentadiene, which will be used in this experiment cannot be purchased commercially, so it must be prepare in the lab by thermally cracking dicyclopentadiene. The reason cyclopentadiene is not commercially available is due to that fact that on standing, two molecules of cyclopentadiene react with one another via a [4 2] cycloaddition to produce dicyclopentadiene (figure 7a). To obtain cyclopentadiene for your experiment, it will be necessary to thermally crack dicyclopentadiene to produce two molecules of cyclopentadiene Experiment 22 The Diels-Alder Cycloaddition Reaction pg. 2

3 as shown in figure 7b. This thermal cracking is merely the reverse of the Diels-Alder reaction, thus it is called a Retro Diels-Alder reaction. The cracking process requires a very high temperature of 300 C. (a) = cyclopentadiene dicyclopentadiene (b) High Heat Retro Diels-Alder 2 Figure 7: Cyclopentadiene Dimerization and Cracking Dicyclopentadiene B. Experimental Procedure Cracking Dicyclopentadiene to btain Cyclopentadiene As discussed in the introduction, cyclopentadiene must be obtained by cracking dicyclopentadiene. The cracking is carried out at 300 C. Do not use a thermometer in the aluminum block as the thermometers in our lab do not go up to this temperature and will break under the high temperatures conditions employed. It is only necessary that two cracking apparatuses be set up in each lab. This will be enough to provide cyclopentadiene for every student. Set up the cracking apparatus as shown in figure 8. To the 5 ml conical reaction vial, add approximately 2 ml of paraffin oil and a spin vane. nce assembled, support the entire assembly with a clamp. Before heating, check the following: All screw connections should be secure. The side-arm of the Claisen head should be sealed with a septum and a screw cap. The side-arm of the Hickman still should be closed off with a screw cap. Turn the hot-plate to high and allow the apparatus to heat up for 10 min. At this point, the paraffin oil should be at approximately 300 C, which is the temperature necessary to crack dicyclopentadiene. Fill the cold finger with ice water using a pipet. Be sure to periodically replace the ice water to ensure the cold finger stays cold during the entire cracking process. Fit a syringe with a needle and fill the syringe with dicyclopentadiene. Insert the needle through the septum on the Claisen head and slowly add the dicyclopentadiene. The cracking process is rapid and you should be able to observe the cyclopentadiene (bp 42 C) being collected in the Hickman still. nce a fair amount of cyclopentadiene has been collected, the side-arm can be uncapped and the solution transferred to a small vial via pipet. At this time, you may begin using the cyclopentadiene for the second part of the experiment. Continue to add dicyclopentadiene via syringe until enough cyclopentadiene has been collected for everyone to perform the second part of the experiment. hen finished, turn off the heat and allow the apparatus to cool before disassembly. Return the cleaned Hickman still to your TA at the end of lab. Do not lock it in your drawer! Experiment 22 The Diels-Alder Cycloaddition Reaction pg. 3

4 cold finger adapter Hickman still cap clamp here air condenser Dicyclopentadiene will be continuously added as needed by syringing it into the vial through the septum. septum Claisen head vial heating block hot plate Figure 8. Cracking Apparatus Diels-Alder Reaction of Cyclopentadiene with Maleic Anhydride This particular Diels-Alder reaction is rapid at room temperature. To aid in product isolation, the entire reaction will be conducted in the Craig tube. To the Craig tube, add 0.8 ml of reagent grade ethyl acetate and 175 mg of maleic anhydride. Stir the solution until the solid has dissolved. Add 0.8 ml of reagent grade hexane and mix well. Next, add 140 mg of cyclopentadiene. ait for approximately 5 min then scratch the walls of the Craig tube to initiate crystallization. Cool the solution in an ice-bath and collect the crystals by centrifugation. Empty the crystals onto a pre-weighed watch glass. Determine the yield and melting point of the isolated product. Experiment 22 The Diels-Alder Cycloaddition Reaction pg. 4

5 C. Pre-Lab Questions 1. If the Diels-Alder reaction is classified as a [4 2] cycloaddition reaction, how would you classify the cycloaddition reactions shown below? (a) S S (b) 2. You are instructed to use 140 mg of cyclopentadiene (d = 0.80 g/ml). It is typically more convenient to measure out a volume of liquid. hat volume of cyclopentadiene should be used? 3. In the Diels-Alder reaction that you will be performing, which reagent will be limiting? Cyclopentadiene or maleic anhydride? Show your work! 4. Is it possible for the diene shown below to undergo a Diels-Alder reaction with maleic anhydride? Explain. D. Post-Lab Questions 1. hat do you suspect would have happened if 1.6 ml of ethyl acetate were used as the reaction solvent as opposed to 0.8 ml of ethyl acetate and 0.8 ml of hexane? Hint: refer to the crystallization experiment. 2. Paraffin oil has a boiling point greater than 370 C. hat was the purpose of adding paraffin to the reaction flask when cracking dicyclopentadiene? 3. Give the structure of the product for each Diels-Alder reaction shown below. C 2 CH 3 C 2 CH 3 4. If you had conducted the reaction in a conical vial and then collected the crystals using a Hirsch Funnel, how do you think your percent yield would have changed? Explain. Experiment 22 The Diels-Alder Cycloaddition Reaction pg. 5